Cancer is a major worldwide public health problem; in the United States alone, approximately 560,000 people died of cancer in 2006. See, e.g., U.S. Mortality Data 2006, National Center for Health Statistics, Centers for Disease Control and Prevention (2009). Many types of cancer have been described in the medical literature. Examples include cancer of blood, bone, skin, lung, colon, breast, prostate, ovary, brain, kidney, bladder, pancreas, and liver, among others. The incidence of cancer continues to climb as the general population ages and as new forms of cancer develop. A continuing need exists for effective therapies to treat subjects with cancer.
Non-small cell lung cancer (NSCLC) is a heterogeneous aggregate of histologies, including, e.g., epidermoid or squamous carcinoma, adenocarcinoma, and large cell carcinoma. Patients with NSCLC may be divided into three groups that reflect both the extent of the disease and the treatment approach: (1) patients with tumors that are surgically resectable; (2) patients with either locally or regionally advanced lung cancer; and (3) patients with distant metastases at the time of diagnosis. Current treatments for NSCLC include surgery, chemotherapy, and/or radiation therapy. As indicated by the National Cancer Institute, however, current methods of treating NSCLC are often unsatisfactory, and a need exists for effective therapies to treat subjects with NSCLC. See, e.g., Non-Small Cell Lung Cancer Treatment (PDQ®), U.S. National Institutes of Health, National Cancer Institute, available at http://www.cancer.gov.
Nucleoside analogs have been tested clinically for the treatment of certain cancers. The nucleoside analogs 5-azacytidine (also known as 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one; National Service Center designation NSC-102816; CAS Registry Number 320-67-2; azacitidine; Aza and AZA; and currently marketed as VIDAZA®) and 2′-deoxy-5-azacytidine (also known as 5-aza-2′-deoxycytidine, decitabine, Dac, and DAC, and currently marketed as DACOGEN®) are DNA methyltransferase (DNMT) inhibitors that have been approved by the U.S. Food and Drug Administration for the treatment of myelodysplastic syndromes (MDS). Azacitidine and decitabine are cytidine analogs; a structural difference between these cytidine analogs and their related natural nucleosides is the presence of a nitrogen at position 5 of the cytosine ring in place of a carbon. Azacitidine may be defined as having a molecular formula of C8H12N4O5, a molecular weight of 244.21 grams per mole, and a structure as shown below. Decitabine may be defined as having a molecular formula of C8H12N4O4, a molecular weight of 228.21 grams per mole, and a structure as shown below.

Azacitidine and decitabine have been tested in clinical trials and showed significant anti-tumor activity, such as, for example, in the treatment of myelodysplastic syndromes (MDS), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphocytic leukemia (ALL), and non Hodgkin's lymphoma (NHL). See, e.g., Aparicio et al., Curr. Opin. Invest. Drugs 3(4): 627-33 (2002). Azacitidine has undergone NCI-sponsored trials for the treatment of MDS and has been approved for treating all FAB subtypes of MDS. See, e.g., Kornblith et al., J. Clin. Oncol. 20(10): 2441-52 (2002); Silverman et al., J. Clin. Oncol. 20(10): 2429-40 (2002). Azacitidine may alter the natural course of MDS by diminishing the transformation to AML through its cytotoxic activity and its inhibition of DNA methyltransferase. In a Phase III study, azacitidine significantly prolonged survival and time to AML transformation or death in elderly subjects. See, e.g., Silverman et al., Blood 106(11): Abstract 2526 (2005).